TY - JOUR
T1 - Variation in upstream open reading frames contributes to allelic diversity in maize protein abundance
AU - Gage, Joseph L.
AU - Mali, Sujina
AU - McLoughlin, Fionn
AU - Khaipho-Burch, Merritt
AU - Monier, Brandon
AU - Bailey-Serres, Julia
AU - Vierstra, Richard D.
AU - Buckler, Edward S.
N1 - Funding Information:
ACKNOWLEDGMENTS. This material is based upon work supported by the NSF Postdoctoral Research Fellowship in Biology under Grant IOS-1906619, NSF Grant IOS-1840687, NSF Grant IOS-1822330, and the US Department of Agriculture Agricultural Research Service.
Publisher Copyright:
Copyright © 2022 the Author(s).
PY - 2022/4/5
Y1 - 2022/4/5
N2 - The 5′ untranslated region (UTR) sequence of eukaryotic mRNAs may contain upstream open reading frames (uORFs), which can regulate translation of the main ORF (mORF). The current model of translational regulation by uORFs posits that when a ribosome scans a mRNA and encounters an uORF, translation of that uORF can prevent ribosomes from reaching the mORF and cause decreased mORF translation. In this study, we first observed that rare variants in the 5′ UTR dysregulate maize (Zea mays L.) protein abundance. Upon further investigation, we found that rare variants near the start codon of uORFs can repress or derepress mORF translation, causing allelic changes in protein abundance. This finding holds for common variants as well, and common variants that modify uORF start codons also contribute disproportionately to metabolic and whole-plant phenotypes, suggesting that translational regulation by uORFs serves an adaptive function. These results provide evidence for the mechanisms by which natural sequence variation modulates gene expression, and ultimately, phenotype.
AB - The 5′ untranslated region (UTR) sequence of eukaryotic mRNAs may contain upstream open reading frames (uORFs), which can regulate translation of the main ORF (mORF). The current model of translational regulation by uORFs posits that when a ribosome scans a mRNA and encounters an uORF, translation of that uORF can prevent ribosomes from reaching the mORF and cause decreased mORF translation. In this study, we first observed that rare variants in the 5′ UTR dysregulate maize (Zea mays L.) protein abundance. Upon further investigation, we found that rare variants near the start codon of uORFs can repress or derepress mORF translation, causing allelic changes in protein abundance. This finding holds for common variants as well, and common variants that modify uORF start codons also contribute disproportionately to metabolic and whole-plant phenotypes, suggesting that translational regulation by uORFs serves an adaptive function. These results provide evidence for the mechanisms by which natural sequence variation modulates gene expression, and ultimately, phenotype.
KW - gene expression
KW - maize
KW - proteome
KW - rare alleles
KW - uORF
UR - http://www.scopus.com/inward/record.url?scp=85127225866&partnerID=8YFLogxK
U2 - 10.1073/pnas.2112516119
DO - 10.1073/pnas.2112516119
M3 - Article
C2 - 35349347
AN - SCOPUS:85127225866
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
M1 - e2112516119
ER -